Pompilid wasp-derived neuropeptides

ABSTRACT

The present invention provides a peptide represented by the amino acid sequence formula (A): 
     
       
         H-X 1 -X 2 -X 3 -X 4 -Gly-X 6 -X 7 -Asp-Gln-R  (A) 
       
     
     wherein: 
     each of X 1  and X 3  independently represents Arg or Lys, each of X 2 , X 4  and X 6  independently represents Ile or Leu, and X 7  represents Phe, Tyr or Trp; and 
     R represents -NH 2 , -Leu-NH 2 , -Leu-Ser-NH 2 , -Leu-Ser-Lys-NH 2 , -Leu-Ser-Arg-NH 2 , -Leu-Ser-Lys-Leu-NH 2 , or -Leu-Ser-Arg-Leu-NH 2 ; 
     and a salt thereof. 
     (In the above, Gly stands for a glycine residue, Asp stands for an aspartic acid residue, Gln stands for a glutamine residue, Arg stands for an arginine residue, Lys stands for a lysine residue, Ile stands for an isoleucine residue, Leu stands for a leucine residue, Phe stands for a phenylalanine residue, Tyr stands for a tyrosine residue, Trp stands for a tryptophan residue, and Ser stands for a serine residue.) 
     The peptide acts on glutamate receptors and is expected to be useful in the treatment of cerebral nerve diseases associated with glutamic acid.

This application is a 371 of PCT/JP98/03730, filed Aug. 24, 1998, which claims the priority of Japan JP9-241699, filed Aug. 25, 1997

TECHNICAL FIELD

The present invention relates to novel neuropeptides and more specifically to peptides obtained from the venoms of the solitary wasps Anoplius samariensis and Batozonellus maculifrons, and analogous peptides thereof.

BACKGROUND ART

Since solitary wasp species such as thread-waisted wasps and pompilid wasps paralyze other insects with their venom, it is believed that the venom contain substances that act on the nervous system. In fact, peptides called mastoparans have been isolated from a certain kind of solitary wasp, and these peptides are used as useful compounds for the study of information transmission system of the living body.

On the other hand, various compounds have been isolated in the studies on spider toxins, and it has been confirmed that their effect of paralyzing nerves is based on their inhibitory action on glutamate receptors. Glutamic acid is known to play an important role as an excitatory neurotransmitter mediated by glutamate receptors in the central nervous system (e.g. brain, spinal cord) of mammals, and the synapses of insects and crustaceans. And further, it is known that excess glutamic acid causes over-excitation of nerve cells resulting in death of the nerve cells. Therefore, enhancement of the function of glutamate receptors and conversely temporary blocking of their function are believed to provide therapeutic benefits on cerebral nerve diseases associated with glutamic acid.

DISCLOSURE OF THE INVENTION

Accordingly, the object of the present invention is to find, in the venom of the solitary wasps, substances that act on the glutamate receptor or substances that promote or inhibit the release of glutamic acid, and to apply them to medical therapeutic purposes.

In order to achieve the above object, the present inventors have isolated a peptide (1) represented by SEQ ID NO: 1:

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂  (1)

and a peptide (97) represented by SEQ ID NO: 2:

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂  (97)

from the venom sac extracts of solitary wasps A. samariensis and B. maculifrons, on the basis of the ability to enhance or block the neurotransmission through the neuron synapses of lobster's walking leg.

Furthermore, peptides related to the above peptides (1) and (97) were synthesized by the conventional solid phase method and their structure-activity relationship was examined. As a result, it was found that the peptides represented by the amino acid sequence formula (A):

H-X₁-X₂-X₃-X₄-Gly-X₆-X₇-Asp-Gln-R  (A)

wherein:

R is basically NH_(2,) which also may be -Leu-NH₂, -Leu-Ser-NH₂, -Leu-Ser-Lys-NH₂, -Leu-Ser-Arg-NH₂, -Leu-Ser-Lys-Leu-NH₂, (SEQ ID NO:3) or -Leu-Ser-Arg-Leu-NH₂ (SEQ ID NO:4),

X₁ and X₃ are basic amino acid residues;

X₂, X₄ and X₆ are aliphatic amino acid residues; and

X₇ is an aromatic amino acid residue, can show the above-mentioned activity.

The basic amino acid residues X₁ and X₃ include arginine or lysine residue, the aliphatic amino acid residues X₂, X₄ and X₆ include leucine or isoleucine residue, and the aromatic amino acid residue X₇ includes phenylalanine, tyrosine, or tryptophan residue.

Accordingly, the present invention provides, as a neuro-peptide, a peptide represented by the amino acid sequence formula (A):

H-X₁-X₂-X₃-X₄-Gly-X₆-X₇-Asp-Gln-R  (A)

wherein:

each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp; and

R represents —NH₂, -Leu-NH₂, -Leu-Ser-NH₂, -Leu-Ser-Lys-NH₂, -Leu-Ser-Arg-NH₂, -Leu-Ser-Lys-Leu-NH₂, (SEQ ID NO:3) or -Leu-Ser-Arg-Leu-NH₂ (SEQ ID NO:4);

and a salt thereof.

As an embodiment, the present invention provides a peptide represented by the amino acid sequence formula (B):

H-X₁-X₂-X₃-X₄-Gly-X₆-X₇-Asp-Gln-NH₂  (B)

wherein:

each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp;

and a salt thereof.

As another embodiment, the present invention provides a peptide represented by the amino acid sequence formula (C):

H-X₁-X₂-X₃-X₄-Gly-X₆-X₇-Asp-Gln-Leu-NH₂(C)  (SEQ ID NO:200)

wherein:

each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp;

and a salt thereof.

As a further embodiment, the present invention provides a peptide represented by the amino acid sequence formula (D):

H-X₁-X₂-X₃-X₄-Gly-X₆-X₇-Asp-Gln-Leu-Ser-NH₂(D)  (SEQ ID NO:199)

wherein:

each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp;

and a salt thereof.

As still another embodiment, the present invention provides a peptide represented by the amino acid sequence formula (E):

H-X₁-X₂-X₃-X₄-Gly-X₆-X₇-Asp-Gln-Leu-Ser-Lys-NH₂(E)  (SEQ ID NO:5)

wherein:

each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp;

and a salt thereof.

As still another embodiment, the present invention provides a peptide represented by the amino acid sequence formula (F):

H-X₁-X₂-X₃-X₄-Gly-X₆-X₇-Asp-Gln-Leu-Ser-Arg-NH₂(F)  (SEQ ID NO:6)

wherein:

each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp;

and a salt thereof.

As still another embodiment, the present invention provides a peptide represented by the amino acid sequence formula (G):

H-X₁-X₂-X₃-X₄-Gly-X₆-X₇-Asp-Gln-Leu-Ser-Lys-Leu-NH₂(G)  (SEQ ID NO:7)

wherein:

each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp;

and a salt thereof.

As still a further embodiment, the present invention provides a peptide represented by the amino acid sequence formula (H):

H-X₁-X₂-X₃-X₄-Gly-X₆-X₇-Asp-Gln-Leu-Ser-Arg-Leu-NH₂(H)  (SEQ ID NO:8)

wherein:

each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp;

and a salt thereof.

Among the above peptides provided by the present invention, the most preferred embodiment is a peptide represented by the amino acid sequence formula (1):

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂(1)  (SEQ ID NO:1)

and a salt thereof, or a peptide represented by the amino acid sequence formula (97):

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂(97)  (SEQ ID NO:2)

and a salt thereof.

As another embodiment, the present invention provides a pharmaceutical composition containing the peptide represented by the amino acid sequence formula (A) or a salt thereof for treatment of glutamate receptor related diseases.

As still another embodiment, the present invention provides use of the peptide represented by the amino acid sequence formula (A) or a salt thereof for treatment of glutamate receptor related diseases.

As still a further embodiment, the present invention provides a method for treatment of glutamate receptor related diseases which composing administering an effective amount of the peptide represented by the amino acid sequence formula (A) or a salt thereof.

BEST MODE FOR CARRYING OUT THE INVENTION

In the present specification and in each of the above formulae, Gly stands for a glycine residue, Asp stands for an aspartic acid residue, Gln stands for a glutamine residue, Arg stands for an arginine residue, Lys stands for a lysine residue, Ile stands for an isoleucine residue, Leu stands for a leucine residue, Phe stands for a phenylalanine residue, Tyr stands for a tyrosine residue, Trp stands for a tryptophan residue, and Ser stands for a serine residue. Amino acid sequences are indicated by the triplet code of IUPAC.

The peptides provided by the present invention include the following peptides:

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (1) (SEQ ID NO:1)

H-Arg-Ile-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (2) (SEQ ID NO:9)

H-Arg-Ile-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (3) (SEQ ID NO:10)

H-Arg-Ile-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (4) (SEQ ID NO:11)

H-Arg-Ile-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (5) (SEQ ID NO:12)

H-Arg-Ile-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (6) (SEQ ID NO:13)

H-Arg-Ile-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (7) (SEQ ID NO:14)

H-Arg-Ile-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (8) (SEQ ID NO:15)

H-Arg-Ile-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (9) (SEQ ID NO:16)

H-Arg-Ile-Lys-Leu-Gly-leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (10) (SEQ ID NO:17)

H-Arg-Ile-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (11) (SEQ ID NO:18)

H-Arg-Ile-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (12) (SEQ ID NO:19)

H-Arg-Ile-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (13) (SEQ ID NO:20)

H-Arg-Ile-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (14) (SEQ ID NO:21)

H-Arg-Ile-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (15) (SEQ ID NO:22)

H-Arg-Ile-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (16) (SEQ ID NO:23)

H-Arg-Ile-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (17) (SEQ ID NO:24)

H-Arg-Ile-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (18) (SEQ ID NO:25)

H-Arg-Ile-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (19) (SEQ ID NO:26)

H-Arg-Ile-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (20) (SEQ ID NO:27)

H-Arg-Ile-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (21) (SEQ ID NO:28)

H-Arg-Ile-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (22) (SEQ ID NO:29)

H-Arg-Ile-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (23) (SEQ ID NO:30)

H-Arg-Ile-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (24) (SEQ ID NO:31)

H-Arg-Leu-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (25) (SEQ ID NO:32)

H-Arg-Leu-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (26) (SEQ ID NO:33)

H-Arg-Leu-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (27) (SEQ ID NO:34)

H-Arg-Leu-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (28) (SEQ ID NO:35)

H-Arg-Leu-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (29) (SEQ ID NO:36)

H-Arg-Leu-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (30) (SEQ ID NO:37)

H-Arg-Leu-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (31) (SEQ ID NO:38)

H-Arg-Leu-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (32) (SEQ ID NO:39)

H-Arg-Leu-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (33) (SEQ ID NO:40)

H-Arg-Leu-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (34) (SEQ ID NO:41)

H-Arg-Leu-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (35) (SEQ ID NO:42)

H-Arg-Leu-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (36) (SEQ ID NO:43)

H-Arg-Leu-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (37) (SEQ ID NO:44)

H-Arg-Leu-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (38) (SEQ ID NO:45)

H-Arg-Leu-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (39) (SEQ ID NO:46)

H-Arg-Leu-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (40) (SEQ ID NO:47)

H-Arg-Leu-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (41) (SEQ ID NO:48)

H-Arg-Leu-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (42) (SEQ ID NO:49)

H-Arg-Leu-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (43) (SEQ ID NO:50)

H-Arg-Leu-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (44) (SEQ ID NO:51)

H-Arg-Leu-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-MH₂ (45) (SEQ ID NO:52)

H-Arg-Leu-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (46) (SEQ ID NO:53)

H-Arg-Leu-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (47) (SEQ ID NO:54)

H-Arg-Leu-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (48) (SEQ ID NO:55)

H-Lys-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (49) (SEQ ID NO:56)

H-Lys-Ile-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (50) (SEQ ID NO:57)

H-Lys-Ile-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (51) (SEQ ID NO:58)

H-Lys-Ile-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (52) (SEQ ID NO:59)

H-Lys-Ile-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (53) (SEQ ID NO:60)

H-Lys-Ile-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (54) (SEQ ID NO:61)

H-Lys-Ile-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (55) (SEQ ID NO:62)

H-Lys-Ile-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (56) (SEQ ID NO:63)

H-Lys-Ile-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (57) (SEQ ID NO:64)

H-Lys-Ile-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu NH₂ (58) (SEQ ID NO:65)

H-Lys-Ile-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (59) (SEQ ID NO:66)

H-Lys-Ile-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (60) (SEQ ID NO:67)

H-Lys-Ile-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (61) (SEQ ID NO:68)

H-Lys-Ile-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (62) (SEQ ID NO:69)

H-Lys-Ile-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (63) (SEQ ID NO:70)

H-Lys-Ile-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (64) (SEQ ID NO:71)

H-Lys-Ile-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (65) (SEQ ID NO:72)

H-Lys-Ile-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (66) (SEQ ID NO:73)

H-Lys-Ile-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (67) (SEQ ID NO:74)

H-Lys-Ile-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (68) (SEQ ID NO:75)

H-Lys-Ile-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (69) (SEQ ID NO:76)

H-Lys-Ile-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (70) (SEQ ID NO:77)

H-Lys-Ile-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (71) (SEQ ID NO:78)

H-Lys-Ile-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (72) (SEQ ID NO:79)

H-Lys-Leu-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (73) (SEQ ID NO:80)

H-Lys-Leu-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (74) (SEQ ID NO:81)

H-Lys-Leu-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (75) (SEQ ID NO:82)

H-Lys-Leu-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (76) (SEQ ID NO:83)

H-Lys-Leu-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (77) (SEQ ID NO:84)

H-Lys-Leu-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (78) (SEQ ID NO:85)

H-Lys-Leu-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (79) (SEQ ID NO:86)

H-Lys-Leu-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (80) (SEQ ID NO:87)

H-Lys-Leu-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (81) (SEQ ID NO:88)

H-Lys-Leu-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (82) (SEQ ID NO:89)

H-Lys-Leu-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (83) (SEQ ID NO:90)

H-Lys-Leu-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (84) (SEQ ID NO:91)

H-Lys-Leu-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (85) (SEQ ID NO:92)

H-Lys-Leu-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (86) (SEQ ID NO:93)

H-Lys-Leu-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (87) (SEQ ID NO:94)

H-Lys-Leu-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (88) (SEQ ID NO:95)

H-Lys-Leu-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (89) (SEQ ID NO:96)

H-Lys-Leu-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (90) (SEQ ID NO:97)

H-Lys-Leu-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (91) (SEQ ID NO:98)

H-Lys-Leu-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (92) (SEQ ID NO:99)

H-Lys-Leu-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (93) (SEQ ID NO:100)

H-Lys-Leu-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (94) (SEQ ID NO:101)

H-Lys-Leu-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (95) (SEQ ID NO:102)

H-Lys-Leu-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ (96) (SEQ ID NO:103)

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (97) (SEQ ID NO:104)

H-Arg-Ile-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (98) (SEQ ID NO:105)

H-Arg-Ile-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (99) (SEQ ID NO:106)

H-Arg-Ile-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (100) (SEQ ID NO:107)

H-Arg-Ile-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (101) (SEQ ID NO:108)

H-Arg-Ile-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (102) (SEQ ID NO:109)

H-Arg-Ile-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (103) (SEQ ID NO:110)

H-Arg-Ile-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (104) (SEQ ID NO:111)

H-Arg-Ile-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (105) (SEQ ID NO:112)

H-Arg-Ile-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (106) (SEQ ID NO:113)

H-Arg-Ile-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (107) (SEQ ID NO:114)

H-Arg-Ile-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (108) (SEQ ID NO:115)

H-Arg-Ile-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (109) (SEQ ID NO:116)

H-Arg-Ile-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (110) (SEQ ID NO:117)

H-Arg-Ile-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (111) (SEQ ID NO:118)

H-Arg-Ile-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (112) (SEQ ID NO:119)

H-Arg-Ile-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (113) (SEQ ID NO:120)

H-Arg-Ile-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (114) (SEQ ID NO:121)

H-Arg-Ile-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (115) (SEQ ID NO:122)

H-Arg-Ile-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (116) (SEQ ID NO:123)

H-Arg-Ile-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (117) (SEQ ID NO:124)

H-Arg-Ile-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (118) (SEQ ID NO:125)

H-Arg-Ile-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Let-NH₂ (119) (SEQ ID NO:126)

H-Arg-Ile-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (120) (SEQ ID NO:127)

H-Arg-Leu-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (121) (SEQ ID NO:128)

H-Arg-Leu-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (122) (SEQ ID NO:129)

H-Arg-Leu-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (123) (SEQ ID NO:130)

H-Arg-Leu-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (124) (SEQ ID NO:131)

H-Arg-Leu-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (125) (SEQ ID NO:132)

H-Arg-Leu-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (126) (SEQ ID NO:133)

H-Arg-Leu-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (127) (SEQ ID NO:134)

H-Arg-Leu-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (128) (SEQ ID NO:135)

H-Arg-Leu-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (129) (SEQ ID NO:136)

H-Arg-Leu-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (130) (SEQ ID NO:137)

H-Arg-Leu-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (131) (SEQ ID NO:138)

H-Arg-Leu-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (132) (SEQ ID NO:139)

H-Arg-Leu-Lys-Leu-Gly-LIe-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (133) (SEQ ID NO:140)

H-Arg-Leu-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (134) (SEQ ID NO:141)

H-Arg-Leu-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (135) (SEQ ID NO:142)

H-Arg-Leu-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (136) (SEQ ID NO:143)

H-Arg-Leu-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (137) (SEQ ID NO:144)

H-Arg-Leu-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (138) (SEQ ID NO:145)

H-Arg-Leu-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (139) (SEQ ID NO:146)

H-Arg-Leu-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (140) (SEQ ID NO:147)

H-Arg-Leu-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (141) (SEQ ID NO:148)

H-Arg-Leu-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (142) (SEQ ID NO:149)

H-Arg-Leu-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (143) (SEQ ID NO:150)

H-Arg-Leu-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (144) (SEQ ID NO:151)

H-Lys-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (145) (SEQ ID NO:152)

H-Lys-Ile-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (146) (SEQ ID NO:153)

H-Lys-Ile-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (147) (SEQ ID NO:154)

H-Lys-Ile-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (148) (SEQ ID NO:155)

H-Lys-Ile-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (149) (SEQ ID NO:156)

H-Lys-Ile-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (150) (SEQ ID NO:157)

H-Lys-Ile-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (151) (SEQ ID NO:158)

H-Lys-Ile-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (152) (SEQ ID NO:159)

H-Lys-Ile-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (153) (SEQ ID NO:160)

H-Lys-Ile-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (154) (SEQ ID NO:161)

H-Lys-Ile-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (155) (SEQ ID NO:162)

H-Lys-Ile-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (156) (SEQ ID NO:163)

H-Lys-Ile-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (157) (SEQ ID NO:164)

H-Lys-Ile-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (158) (SEQ ID NO:165)

H-Lys-Ile-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (159) (SEQ ID NO:166)

H-Lys-Ile-Arg-Ile-Gly-ILe-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (160) (SEQ ID NO:167)

H-Lys-Ile-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (161) (SEQ ID NO:168)

H-Lys-Ile-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu NH₂ (162) (SEQ ID NO:169)

H-Lys-Ile-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (163) (SEQ ID NO:170)

H-Lys-Ile-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (164) (SEQ ID NO:171)

H-Lys-Ile-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (165) (SEQ ID NO:172)

H-Lys-Ile-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (166) (SEQ ID NO:173)

H-Lys-Ile-Arg-Leu-Gly-LIe-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (167) (SEQ ID NO:174)

H-Lys-Ile-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (168) (SEQ ID NO:175)

H-Lys-Leu-Lys-ILe-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (169) (SEQ ID NO:176)

H-Lys-Leu-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (170) (SEQ ID NO:177)

H-Lys-Leu-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (171) (SEQ ID NO:178)

H-Lys-Leu-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (172) (SEQ ID NO:179)

H-Lys-Leu-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (173) (SEQ ID NO:180)

H-Lys-Leu-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (174) (SEQ ID NO:181)

H-Lys-Leu-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (175) (SEQ ID NO:182)

H-Lys-Leu-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (176) (SEQ ID NO:183)

H-Lys-Leu-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (177) (SEQ ID NO:184)

H-Lys-Leu-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (178) (SEQ ID NO:185)

H-Lys-Leu-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (179) (SEQ ID NO:186)

H-Lys-Leu-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (180) (SEQ ID NO:187)

H-Lys-Leu-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (181) (SEQ ID NO:188)

H-Lys-Leu-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (182) (SEQ ID NO:189)

H-Lys-Leu-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (183) (SEQ ID NO:190)

H-Lys-Leu-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (184) (SEQ ID NO:191)

H-Lys-Leu-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (185) (SEQ ID NO:192)

H-Lys-Leu-Arg-ILe-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (186) (SEQ ID NO:193)

H-Lys-Leu-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (187) (SEQ ID NO:194)

H-Lys-Leu-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (188) (SEQ ID NO:195)

H-Lys-Leu-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (189) (SEQ ID NO:196)

H-Lys-Leu-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (190) (SEQ ID NO:197)

H-Lys-Leu-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (191) (SEQ ID NO:198)

H-Lys-Leu-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ (192) (SEQ ID NO:199)

In order to obtain the peptides of the present invention, for example, venom sac of a solitary wasp containing said peptides may be excised and then homogenized in a water-containing organic solvent, and the resulting homogenate may be centrifuged to obtain a supernatant, which may be purified by a reversed phase chromatography until finally it exhibits a single peak when monitored by UV absorbance at 215 nm, thereby isolating and purifying the desired compound.

The water-containing organic solvent to be used for the homogenization during the above purification process means a mixture of water and an organic solvent that is freely miscible with water, and may be any solvent which permits extraction of the compound of the present invention. Examples include, but not limited to, water-containing acetone, water-containing acetonitrile, and the like. When the resulting supernatant is directly applied to the reversed phase chromatography, it is preferred that about 0.1% of trifluoroacetic acid (hereinafter referred to as TFA) is added to such a water-containing organic solvent.

Since the peptides provided by the present invention consist of at most about 13 amino acids, they can be synthesized by the conventional liquid or solid phase method. Furthermore, since the peptides of the present invention are basic peptides, they can be converted to appropriate acid-added salts according to conventional technique. Such preferred acid-added salts may be obtained by reaction with a pharmaceutically acceptable acid, and said salts include, for example, lactates, acetates, succinates, maleates, fumarates, tartarates, citrates, gluconates, ascorbates, benzoates, methanesulfonates, cinnamates, benzenesulfonates or phosphates, hydrogenphosphates, hydrochlorides, hydrobromides, hydroiodides, sulfamates, sulfates, trifluoroacetates, and the like.

The biological activity of the present peptides can be assayed according to the methods described in Japanese Patent Laid-Open No. 4-198161, in which excitatory postsynaptic potential (EPSP) is generated in the neuromuscular specimen of a lobster's walking leg, and the effect of the compound given to the nerve fibers on the EPSP is determined.

In general, substances inhibiting EPSP are believed to be glutamate antagonists or inhibitors for the release of glutamic acid, and the substances enhancing EPSP are believed to be glutamate-like agonists or accelerators for the release of glutamic acid.

As described in the Examples below, the peptides of the present invention show a remarkable effect of enhancing EPSP determined by the above assay. Accordingly, the compounds of the present invention are useful for enhancing cerebral neural activities and recovering muscular strength in the treatment of neuromuscular diseases. They are also useful as a tool for the study of neuroscience toward the elucidation of the transmission mechanism.

The present invention is now illustrated in more detail by way of the following examples, but it is to be noted that the present invention is not limited by these Examples in any way.

EXAMPLE 1 Isolation and Structure Determination of Peptides (1) and (97)

1) Isolation of Peptide (1)

The venom sacs of 60 female Anoplius samariensis were excised and lyophilized. These were homogenized in 1 ml of 50% acetonitrile/water containing 0.1% TFA and then centrifuged to obtain an extract. The precipitate was centrifuged again with 1 ml of 50% acetonitrile/water containing 0.1% TFA. This procedure was then repeated four times. All the extracts resulting from the above procedure carried out five times in total were collected and then evaporated under reduced pressure to obtain a crude extract.

The resulting crude extract was dissolved in water and then subjected to reversed phase HPLC (Waters Associates) using CAPCELL PAK C₁₈ φ 10 mm×250 mm (Shiseido Co., Ltd.,) with linear gradient from 5% to 95% acetonitrile/water containing 0.1% TFA at a flow rate of 2.5 ml/min over 30 minutes at room temperature. The peak fraction at a retention time of 19 min was collected by monitoring UV absorbance at 215 nm.

The obtained peak fraction was further subjected to HPLC using CAPCELL PAK C₁₈ φ 6 mm×150 mm (Shiseido Co., Ltd.,) with isocratic 29% acetonitrile/water containing 0.1% TFA at a flow rate of 1 ml/min at room temperature, and the peak fraction at a retention time of 15 min was collected by monitoring UV absorbance at 215 nm. This fraction showed a single peak at a retention time of 11 min in HPLC using the above column (isocratic 30% acetonitrile/water containing 0.1% TFA).

The resulting fraction was lyophilized to yield 0.1 mg of peptide (1) as a trifluoroacetate.

2) Isolation of Peptide (97)

The venom sacs of 29 female Batozonellus maculifrons were excised and lyophilized. These were homogenized in 0.5 ml of 50% acetonitrile/water containing 0.1% TFA and then centrifuged to obtain an extract. The precipitate was centrifuged again with 0.5 ml of 50% acetonitrile/water containing 0.1% TFA. This procedure was then repeated four times. All the extracts resulting from the above procedure carried out five times in total were collected and then evaporated under reduced pressure to obtain a crude extract.

The resulting crude extract was dissolved in water and then subjected to reversed phase HPLC using CAPCELL PAK C₁₈ φ 10 mm×250 mm with linear gradient from 5% to 95% acetonitrile/water containing 0.1% TFA at a flow rate of 2.5 ml/min over 30 minutes at room temperature. The peak fraction at a retention time of 19 min was collected by monitoring UV absorbance at 215 nm.

The obtained peak fraction was further subjected to HPLC using CAPCELL PAK C₁₈ φ 6 mm×150 mm with isocratic 29% acetonitrile/water containing 0.1% TFA at a flow rate of 1 ml/min at room temperature, and the peak fractions at a retention time of 15 min and 16 min were collected by monitoring UV absorbance at 215 nm. The fraction obtained at a retention time of 15 min was lyophilized to yield 50 μg of peptide (1) as a trifluoroacetate and the fraction obtained at a retention time of 16 min was lyophilized to yield 30 μg of peptide (97) as atrifluoroacetate.

3) Determination of the Amino Acid Sequence

The amino acid sequences of the resulting peptides were determined by mass spectroscopy and Edman degradation. Mass spectroscopy was conducted by the Ladder sequencing method using carboxypeptidase and aminopeptidase and by MALDI-TOF-MS combined with the CID method. Distinction of Leu from Ile and Lys from Gln was demonstrated by the automatic Edman degradation using ABI 477A/120A Protein Sequencer (Applied Biosystems).

Furthermore, since a peak of m/z=1530 (M+H)⁺ was observed in MALDI-TOF-MS, peptide (1) was found to have a sequence represented by SEQ ID NO: 1 in which the N-terminal is free and the C-terminal is amidated.

On the other hand, peptide (97) was identified with a sequence represented by SEQ ID NO: 2 by observing a peak of m/z=1558 (M+H)⁺ in MALDI-TOF-MS.

EXAMPLE 2 Synthesis of Peptides (1) and (97)

Peptides (1) and (97) were synthesized using TGS-RAM-Resin (Shimadzu Corporation) as a carrier and Fmoc-amino acids in the solid phase method using the automatic peptide synthesizer PSSM-8 (Shimadzu Corporation).

Each of the synthesized peptides was then cleaved from the peptide resin and deprotected by adding a TFA solution containing 5% phenol, 5% thioanisole, 5% water, 3% 1,2-ethanedithiol and 2% ethylmethyl disulfide in an amount of 10 ml per gram of the peptide resin and then treating it at room temperature for 8 hours. After the treatment, ether was added to the TFA solution to precipitate the peptides, and the precipitate was washed three times with ether to obtain crude peptides. The crude peptides were purified by C-18 reversed phase HPLC. The resulting synthetic peptides (1) and (97) showed the same retention time in HPLC, the same mass spectra, and the same biological activity as the natural peptides (1) and (97), respectively.

EXAMPLE 3 Measurement of the Effect on Excitatory Postsynaptic Potential (EPSP)

The effect of the present peptides on excitatory postsynaptic potential (EPSP) was measured according to the method disclosed in Japanese Patent Laid-Open No. 4-198161. Thus, the shell of a lobster's walking leg was removed to expose the excitatory nerve and the inhibitory nerve, and a stimulating electrode was attached thereto. Then the nerve-muscle junction was exposed, and a recording electrode was attached thereto. The walking leg equipped with the electrodes was transferred to a container filled with an artificial seawater, and a partition was set up between the stimulating electrode part and the recording electrode part. The samples to be measured were dissolved into the artificial seawater in the recording electrode side (i.e., the side containing the nerve-muscle junction). Subsequently, the excitatory nerve was electrically stimulated and the EPSP, which was induced by glutamic acid released from the nerve end in response to the stimulation, was recorded.

When the effects of peptides (1) and (97) on EPSP were studied according to this method, peptide (1) enhanced EPSP at a concentration of 1×10⁻⁶ M, and peptide (97) did at 2×10⁻⁷ M.

INDUSTRIAL APPLICABILITY

The peptides provided by the present invention can be used as useful reagents to study the structure-activity relationship of their activities on the glutamate receptor in the field of neuroscience. Furthermore, they can be used as standard compounds in the study of neuroscience, especially in the study of neuropathic diseases such as Huntington's disease, epilepsy, Parkinson's disease and senile dementia, paving the way for pharmaceutical application of substances that act on the glutamate receptor.

203 1 13 PRT Anoplius samariensis 1 Arg Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 2 13 PRT Batozonellus maculifrons 2 Arg Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 3 4 PRT Pompilid sp. 3 Leu Ser Lys Leu 1 4 4 PRT Pompilid sp. 4 Leu Ser Arg Leu 1 5 12 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 5 Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu Ser Lys 1 5 10 6 12 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 6 Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu Ser Arg 1 5 10 7 13 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 7 Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu Ser Lys Leu 1 5 10 8 13 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 8 Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu Ser Arg Leu 1 5 10 9 13 PRT Pompilid sp. 9 Arg Ile Lys Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 10 13 PRT Pompilid sp. 10 Arg Ile Lys Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 11 13 PRT Pompilid sp. 11 Arg Ile Lys Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 12 13 PRT Pompilid sp. 12 Arg Ile Lys Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 13 13 PRT Pompilid sp. 13 Arg Ile Lys Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 14 13 PRT Pompilid sp. 14 Arg Ile Lys Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 15 13 PRT Pompilid sp. 15 Arg Ile Lys Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 16 13 PRT Pompilid sp. 16 Arg Ile Lys Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 17 13 PRT Pompilid sp. 17 Arg Ile Lys Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 18 13 PRT Pompilid sp. 18 Arg Ile Lys Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 19 13 PRT Pompilid sp. 19 Arg Ile Lys Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 20 13 PRT Pompilid sp. 20 Arg Ile Arg Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 21 13 PRT Pompilid sp. 21 Arg Ile Arg Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 22 13 PRT Pompilid sp. 22 Arg Ile Arg Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 23 13 PRT Pompilid sp. 23 Arg Ile Arg Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 24 13 PRT Pompilid sp. 24 Arg Ile Arg Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 25 13 PRT Pompilid sp. 25 Arg Ile Arg Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 26 13 PRT Pompilid sp. 26 Arg Ile Arg Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 27 13 PRT Pompilid sp. 27 Arg Ile Arg Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 28 13 PRT Pompilid sp. 28 Arg Ile Arg Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 29 13 PRT Pompilid sp. 29 Arg Ile Arg Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 30 13 PRT Pompilid sp. 30 Arg Ile Arg Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 31 13 PRT Pompilid sp. 31 Arg Ile Arg Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 32 13 PRT Pompilid sp. 32 Arg Leu Lys Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 33 13 PRT Pompilid sp. 33 Arg Leu Lys Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 34 13 PRT Pompilid sp. 34 Arg Leu Lys Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 35 13 PRT Pompilid sp. 35 Arg Leu Lys Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 36 13 PRT Pompilid sp. 36 Arg Leu Lys Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 37 13 PRT Pompilid sp. 37 Arg Leu Lys Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 38 13 PRT Pompilid sp. 38 Arg Leu Lys Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 39 13 PRT Pompilid sp. 39 Arg Leu Lys Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 40 13 PRT Pompilid sp. 40 Arg Leu Lys Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 41 13 PRT Pompilid sp. 41 Arg Leu Lys Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 42 13 PRT Pompilid sp. 42 Arg Leu Lys Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 43 13 PRT Pompilid sp. 43 Arg Leu Lys Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 44 13 PRT Pompilid sp. 44 Arg Leu Arg Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 45 13 PRT Pompilid sp. 45 Arg Leu Arg Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 46 13 PRT Pompilid sp. 46 Arg Leu Arg Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 47 13 PRT Pompilid sp. 47 Arg Leu Arg Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 48 13 PRT Pompilid sp. 48 Arg Leu Arg Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 49 13 PRT Pompilid sp. 49 Arg Leu Arg Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 50 13 PRT Pompilid sp. 50 Arg Leu Arg Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 51 13 PRT Pompilid sp. 51 Arg Leu Arg Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 52 13 PRT Pompilid sp. 52 Arg Leu Arg Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 53 13 PRT Pompilid sp. 53 Arg Leu Arg Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 54 13 PRT Pompilid sp. 54 Arg Leu Arg Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 55 13 PRT Pompilid sp. 55 Arg Leu Arg Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 56 13 PRT Pompilid sp. 56 Lys Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 57 13 PRT Pompilid sp. 57 Lys Ile Lys Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 58 13 PRT Pompilid sp. 58 Lys Ile Lys Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 59 13 PRT Pompilid sp. 59 Lys Ile Lys Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 60 13 PRT Pompilid sp. 60 Lys Ile Lys Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 61 13 PRT Pompilid sp. 61 Lys Ile Lys Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 62 13 PRT Pompilid sp. 62 Lys Ile Lys Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 63 13 PRT Pompilid sp. 63 Lys Ile Lys Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 64 13 PRT Pompilid sp. 64 Lys Ile Lys Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 65 13 PRT Pompilid sp. 65 Lys Ile Lys Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 66 13 PRT Pompilid sp. 66 Lys Ile Lys Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 67 13 PRT Pompilid sp. 67 Lys Ile Lys Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 68 13 PRT Pompilid sp. 68 Lys Ile Arg Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 69 13 PRT Pompilid sp. 69 Lys Ile Arg Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 70 13 PRT Pompilid sp. 70 Lys Ile Arg Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 71 13 PRT Pompilid sp. 71 Lys Ile Arg Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 72 13 PRT Pompilid sp. 72 Lys Ile Arg Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 73 13 PRT Pompilid sp. 73 Lys Ile Arg Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 74 13 PRT Pompilid sp. 74 Lys Ile Arg Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 75 12 PRT Pompilid sp. 75 Lys Ile Arg Leu Gly Tyr Asp Gln Leu Ser Lys Leu 1 5 10 76 13 PRT Pompilid sp. 76 Lys Ile Arg Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 77 13 PRT Pompilid sp. 77 Lys Ile Arg Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 78 13 PRT Pompilid sp. 78 Lys Ile Arg Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 79 13 PRT Pompilid sp. 79 Lys Ile Arg Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 80 13 PRT Pompilid sp. 80 Lys Leu Lys Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 81 13 PRT Pompilid sp. 81 Lys Leu Lys Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 82 13 PRT Pompilid sp. 82 Lys Leu Lys Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 83 13 PRT Pompilid sp. 83 Lys Leu Lys Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 84 13 PRT Pompilid sp. 84 Lys Leu Lys Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 85 13 PRT Pompilid sp. 85 Lys Leu Lys Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 86 13 PRT Pompilid sp. 86 Lys Leu Lys Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 87 13 PRT Pompilid sp. 87 Lys Leu Lys Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 88 13 PRT Pompilid sp. 88 Lys Leu Lys Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 89 13 PRT Pompilid sp. 89 Lys Leu Lys Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 90 13 PRT Pompilid sp. 90 Lys Leu Lys Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 91 13 PRT Pompilid sp. 91 Lys Leu Lys Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 92 13 PRT Pompilid sp. 92 Lys Leu Arg Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 93 13 PRT Pompilid sp. 93 Lys Leu Arg Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 94 13 PRT Pompilid sp. 94 Lys Leu Arg Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 95 13 PRT Pompilid sp. 95 Lys Leu Arg Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 96 13 PRT Pompilid sp. 96 Lys Leu Arg Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 97 13 PRT Pompilid sp. 97 Lys Leu Arg Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 98 13 PRT Pompilid sp. 98 Lys Leu Arg Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 99 13 PRT Pompilid sp. 99 Lys Leu Arg Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu 1 5 10 100 13 PRT Pompilid sp. 100 Lys Leu Arg Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu 1 5 10 101 13 PRT Pompilid sp. 101 Lys Leu Arg Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu 1 5 10 102 13 PRT Pompilid sp. 102 Lys Leu Arg Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu 1 5 10 103 13 PRT Pompilid sp. 103 Lys Leu Arg Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu 1 5 10 104 13 PRT Pompilid sp. 104 Arg Ile Lys Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 105 13 PRT Pompilid sp. 105 Arg Ile Lys Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 106 13 PRT Pompilid sp. 106 Arg Ile Lys Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 107 13 PRT Pompilid sp. 107 Arg Ile Lys Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 108 13 PRT Pompilid sp. 108 Arg Ile Lys Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 109 13 PRT Pompilid sp. 109 Arg Ile Lys Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 110 13 PRT Pompilid sp. 110 Arg Ile Lys Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 111 13 PRT Pompilid sp. 111 Arg Ile Lys Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 112 13 PRT Pompilid sp. 112 Arg Ile Lys Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 113 13 PRT Pompilid sp. 113 Arg Ile Lys Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 114 13 PRT Pompilid sp. 114 Arg Ile Lys Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 115 13 PRT Pompilid sp. 115 Arg Ile Arg Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 116 13 PRT Pompilid sp. 116 Arg Ile Arg Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 117 13 PRT Pompilid sp. 117 Arg Ile Arg Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 118 13 PRT Pompilid sp. 118 Arg Ile Arg Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 119 13 PRT Pompilid sp. 119 Arg Ile Arg Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 120 13 PRT Pompilid sp. 120 Arg Ile Arg Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 121 13 PRT Pompilid sp. 121 Arg Ile Arg Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 122 13 PRT Pompilid sp. 122 Arg Ile Arg Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 123 13 PRT Pompilid sp. 123 Arg Ile Arg Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 124 13 PRT Pompilid sp. 124 Arg Ile Arg Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 125 13 PRT Pompilid sp. 125 Arg Ile Arg Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 126 13 PRT Pompilid sp. 126 Arg Ile Arg Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 127 13 PRT Pompilid sp. 127 Arg Leu Lys Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 128 13 PRT Pompilid sp. 128 Arg Leu Lys Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 129 13 PRT Pompilid sp. 129 Arg Leu Lys Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 130 13 PRT Pompilid sp. 130 Arg Leu Lys Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 131 13 PRT Pompilid sp. 131 Arg Leu Lys Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 132 13 PRT Pompilid sp. 132 Arg Leu Lys Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 133 13 PRT Pompilid sp. 133 Arg Leu Lys Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 134 13 PRT Pompilid sp. 134 Arg Leu Lys Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 135 13 PRT Pompilid sp. 135 Arg Leu Lys Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 136 13 PRT Pompilid sp. 136 Arg Leu Lys Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 137 13 PRT Pompilid sp. 137 Arg Leu Lys Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 138 13 PRT Pompilid sp. 138 Arg Leu Lys Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 139 13 PRT Pompilid sp. 139 Arg Leu Arg Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 140 13 PRT Pompilid sp. 140 Arg Leu Arg Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 141 13 PRT Pompilid sp. 141 Arg Leu Arg Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 142 13 PRT Pompilid sp. 142 Arg Leu Arg Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 143 13 PRT Pompilid sp. 143 Arg Leu Arg Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 144 13 PRT Pompilid sp. 144 Arg Leu Arg Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 145 13 PRT Pompilid sp. 145 Arg Leu Arg Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 146 13 PRT Pompilid sp. 146 Arg Leu Arg Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 147 13 PRT Pompilid sp. 147 Arg Leu Arg Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 148 13 PRT Pompilid sp. 148 Arg Leu Arg Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 149 13 PRT Pompilid sp. 149 Arg Leu Arg Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 150 13 PRT Pompilid sp. 150 Arg Leu Arg Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 151 13 PRT Pompilid sp. 151 Lys Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 152 13 PRT Pompilid sp. 152 Lys Ile Lys Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 153 13 PRT Pompilid sp. 153 Lys Ile Lys Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 154 13 PRT Pompilid sp. 154 Lys Ile Lys Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 155 13 PRT Pompilid sp. 155 Lys Ile Lys Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 156 13 PRT Pompilid sp. 156 Lys Ile Lys Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 157 13 PRT Pompilid sp. 157 Lys Ile Lys Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 158 13 PRT Pompilid sp. 158 Lys Ile Lys Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 159 13 PRT Pompilid sp. 159 Lys Ile Lys Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 160 13 PRT Pompilid sp. 160 Lys Ile Lys Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 161 13 PRT Pompilid sp. 161 Lys Ile Lys Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 162 13 PRT Pompilid sp. 162 Lys Ile Lys Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 163 13 PRT Pompilid sp. 163 Lys Ile Arg Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 164 13 PRT Pompilid sp. 164 Lys Ile Arg Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 165 13 PRT Pompilid sp. 165 Lys Ile Arg Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 166 13 PRT Pompilid sp. 166 Lys Ile Arg Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 167 13 PRT Pompilid sp. 167 Lys Ile Arg Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 168 13 PRT Pompilid sp. 168 Lys Ile Arg Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 169 13 PRT Pompilid sp. 169 Lys Ile Arg Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 170 13 PRT Pompilid sp. 170 Lys Ile Arg Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 171 13 PRT Pompilid sp. 171 Lys Ile Arg Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 172 13 PRT Pompilid sp. 172 Lys Ile Arg Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 173 13 PRT Pompilid sp. 173 Lys Ile Arg Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 174 13 PRT Pompilid sp. 174 Lys Ile Arg Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 175 13 PRT Pompilid sp. 175 Lys Leu Lys Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 176 13 PRT Pompilid sp. 176 Lys Leu Lys Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 177 13 PRT Pompilid sp. 177 Lys Leu Lys Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 178 13 PRT Pompilid sp. 178 Lys Leu Lys Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 179 13 PRT Pompilid sp. 179 Lys Leu Lys Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 180 13 PRT Pompilid sp. 180 Lys Leu Lys Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 181 13 PRT Pompilid sp. 181 Lys Leu Lys Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 182 13 PRT Pompilid sp. 182 Lys Leu Lys Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 183 13 PRT Pompilid sp. 183 Lys Leu Lys Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 184 13 PRT Pompilid sp. 184 Lys Leu Lys Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 185 13 PRT Pompilid sp. 185 Lys Leu Lys Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 186 13 PRT Pompilid sp. 186 Lys Leu Lys Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 187 13 PRT Pompilid sp. 187 Lys Leu Arg Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 188 13 PRT Pompilid sp. 188 Lys Leu Arg Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 189 13 PRT Pompilid sp. 189 Lys Leu Arg Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 190 13 PRT Pompilid sp. 190 Lys Leu Arg Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 191 13 PRT Pompilid sp. 191 Lys Leu Arg Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 192 13 PRT Pompilid sp. 192 Lys Leu Arg Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 193 13 PRT Pompilid sp. 193 Lys Leu Arg Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 194 13 PRT Pompilid sp. 194 Lys Leu Arg Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu 1 5 10 195 13 PRT Pompilid sp. 195 Lys Leu Arg Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu 1 5 10 196 13 PRT Pompilid sp. 196 Lys Leu Arg Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu 1 5 10 197 13 PRT Pompilid sp. 197 Lys Leu Arg Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu 1 5 10 198 13 PRT Pompilid sp. 198 Lys Leu Arg Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu 1 5 10 199 11 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 199 Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu Ser 1 5 10 200 10 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 200 Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu 1 5 10 201 10 PRT Pompilid sp. misc_feature (1)..(1) Arg or Lys 201 Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Xaa 1 5 10 202 13 PRT Pompilid sp. 202 Arg Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu 1 5 10 203 13 PRT Pompilid sp. 203 Arg Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu 1 5 10 

What is claimed is:
 1. An isolated peptide represented by the following amino acid sequence (SEQ ID NO:201): H-X₁-X₂₋X₃-X₄-Gly-X₆-X₇-Asp-Gln-R wherein: each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp; and R represents -Leu-Ser-Lys-Leu-NH₂ or -Leu-Ser-Arg-Leu-NH₂; and a salt thereof.
 2. The isolated peptide as claimed in claim 1 represented by the following amino acid sequence (SEQ ID NO:7): H-X₁-X₂₋X₃-X₄-Gly-X₆-X₇-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ wherein: each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp; and a salt thereof.
 3. The isolated peptide as claimed in claim 1 represented by the following amino acid sequence (SEQ ID NO:8): H-X₁-X₂₋X₃-X₄-Gly-X₆-X₇-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ wherein: each of X₁ and X₃ independently represents Arg or Lys, each of X₂, X₄ and X₆ independently represents Ile or Leu, and X₇ represents Phe, Tyr or Trp; and a salt thereof.
 4. The isolated peptide as claimed in claim 1 represented by the following amino acid sequence (SEQ ID NO:202): H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH₂ and a salt thereof.
 5. The isolated peptide as claimed in claim 1 represented by the following amino acid sequence (SEQ ID NO:203): H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH₂ and a salt thereof.
 6. The isolated peptide and a salt as claimed in claim 1 as a glutamate receptor agonist. 